FACT’s season of annual meetings is winding down, and as everyone gets back to their homes and day jobs, I hope you have time to rest and reflect on the relationships built and progress made during the past several months. FACT continues to have a presence at the annual meetings of its parent societies, ASBMT and ISCT, and those of other partner organizations, including ASFA, ASGCT, ASH, and SITC. We look forward to participating in the inaugural Cord Blood Connect congress in September, hosted by the Cord Blood Association.

The articles in this newsletter reflect many of the lessons learned and accomplishments made possible by meeting with our colleagues in person at these meetings. Some discussions were complex and nuanced, such as the BMT Time Out commendable practice identified by the FACT Clinical Outcomes Committee and advice on adverse event reporting. Some discussions were intently focused on large tasks, such as review of the draft second edition of the FACT Common Standards in preparation for the public comment period. Other events welcomed new inspectors to the FACT community and celebrated the accomplishments of outgoing Board members.

We appreciate everyone’s participation in the in-person events, and also via volunteer committee teleconferences. Please allow the energy and excitement of these meetings to influence the important work you do on a daily basis.

Congratulations to Dr. Paul Eldridge, FACT Standards Chair, and the FACT-JACIE Standards Committee on publishing the seventh edition FACT-JACIE International Standards for Hematopoietic Cellular Therapy Product Collection, Processing, and Administration on March 1, 2018. The Standards will become effective on May 30, 2018.

Committee Overview

The Foundation for the Accreditation of Cellular Therapy (FACT) has several committees to help FACT achieve its vision of being the premier organization setting standards and awarding accreditation to programs in the evolving field of cellular therapy.

The seventh edition FACT-JACIE Standards Committee is comprised of 58 representatives from around the world who worked for 23 months on the development of the Standards. The committee is divided into four subcommittees: Clinical, Collection, Processing, and Quality Management. The FACT Immune Effector Cell (IEC) Task Force was also involved in the development and review of IEC specific requirements. Everyone’s commitment, expertise, and experience is invaluable to these Standards.

The seventh edition of the Standards contains important additions and changes to requirements to reflect current processes typical in a cellular therapy program. These changes maintain the relevance of the Standards in the field of cellular therapy.

Public Comment Period

During the 90-day public comment period, 653 comments were submitted by 78 contributors residing in 12 different countries. The committee was responsive to public comments and requests made on behalf of related organizations to ensure the seventh edition is broadly accepted throughout the cellular therapy community.

FACT and JACIE greatly appreciate contributors taking the time to review the draft Standards and submit comments.

Accessing the Standards and Other Resources

The Standards, accompanying Accreditation Manual, summary of changes, and crosswalks are available on the FACT website at http://www.factwebsite.org or by using the links provided below:

Dr. Eldridge presented a webinar on how to “Effectively Transition to the 7th Edition Hematopoietic Cellular Therapy Standards” on March 14, 2018. Based on the questions received, a question and answer document was created to assist those who were unable to attend. If you were unable to attend the webinar, you can purchase the recording. FACT inspectors may download the recording for free!

If you have questions related to the seventh edition FACT-JACIE Standards, contact your FACT Coordinator or submit your question to askfact@unmc.edu.

The University of Texas MD Anderson CARTOX Program received accreditation for immune effector cellular therapy by the Foundation for the Accreditation of Cellular Therapy (FACT) at the University of Nebraska Medical Center. The University of Texas MD Anderson CARTOX Program, directed by Elizabeth Shpall, MD, and Sattva S. Neelapu, MD, is the first program to be recognized by FACT for compliance with the new FACT Standards for Immune Effector Cells independent of a bone marrow transplant program. The program received accreditation on April 19, 2018.

Dr. Elizabeth Shpall states, “We are very excited to receive the accreditation for the first stand-alone immune effector cell program. It was a major effort of so many people at MD Anderson to coordinate the many different departments and clinical care teams with such broad expertise. We are very grateful for the FACT IEC Standards which we used extensively as a guide for the development and continued operation of our CARTOX program.”

Dr. Phyllis Warkentin, FACT Chief Medical Officer states, “I welcome the University of Texas MD Anderson CARTOX Program to a network of cellular therapy programs and experts that promote the highest quality in the delivery of cellular therapy and care to the patients they serve. Accredited cellular therapy programs such as the CARTOX program have met rigorous standards and I commend them on this tremendous success.”

FACT is well-served by an involved, conscientious, and inspiring Board of Directors, and two outgoing Board members embodied all of those characteristics. While overcoming the snowstorms that seemed to follow the BMT community, FACT expressed its appreciation to Hugo Fernandez, MD and Gillian Woollett, MA, DPhil during the Board of Directors meeting at the 2018 BMT Tandem Meetings in Salt Lake City.

We look forward to continuing our relationship with these two outstanding individuals, who will no doubt continue to make a difference. Dr. Hernandez and Dr. Woollett, thank you for your service!

Dr. Fernandez’ charge as Chair of the Global Affairs Committee was to provide education, assistance, and a pathway for centers establishing new BMT programs in resource-challenged areas to achieve accreditation. Since 2010, Dr. Fernandez has worked with the committee to identify opportunities to educate the global cell therapy community about the importance of FACT accreditation in establishing quality systems as the foundation for transplant programs.

Thanks to the leadership provided by Dr. Fernandez, FACT now has accredited cell therapy programs located in seven countries (Australia, Brazil, Canada, Mexico, New Zealand, Singapore, and the United States) and counting!

Dr. Woollett leads the FDA Policy and Regulatory Strategy Practice as a Senior Vice President at Avalere and supports clients throughout the healthcare system, from patients’ groups to biopharma companies and payers/providers.

Dr. Woollett has provided a wealth of knowledge and insight to FACT regarding:

The NetCord-FACT Standards define post-processing and post-thaw specifications for cord blood units. When a cord blood unit does not meet post-processing specifications, this is an issue that can be dealt with up front prior to storage. However, cases in which post-thaw specifications are not met are more challenging. At that point, the cord blood unit has likely been selected for a patient in need.

The NetCord-FACT post thaw criteria are >70% viability for CD34 cells, >40% viability for CD45 cells, growth for CFU, and verified identity. Release of a cord blood unit that does not meet this criteria requires exceptional release, a process for which FACT-accredited cord blood banks are required to have a policy or procedure (NetCord-FACT Standard B3.1.24). The policy should outline the process to take when a CB unit does not meet predetermined release criteria, including:

Documenting and investigating the failed criteria, including documentation in the unit record, and

Reporting the deviation to the requesting transplant program prior to distribution.

Agreements with families for private cord blood storage should outline the bank’s processes for nonconforming cord blood units, and the bank must comply with the agreement.

We have noticed an uptick in the number of questions regarding storage in the collection facility. There appears to be a misconception that collection facilities do not store products if the processing facility or a courier picks up the product. However, a product is considered to be in storage when it is not under the immediate control of qualified personnel. For example, a product placed in a transport container waiting to be picked up, even for a short time, is considered to be in storage.

All apheresis collection facilities must have policies or procedures that, regardless of the amount of time the product is stored, address cellular therapy product storage and define every step of the product from the time of collection to the time of release to the courier or processing personnel.

Policies and procedures must address the following in relation to storage:

Defined storage areas and container,

How the integrity and potency of the cellular therapy products are maintained,

The security of the facility,

Facility control of temperature and humidity for storage overnight or longer,

Storage duration, and actions to take if conditions are not met,

Product expiration date and time,

Mechanisms to prevent product release until release criteria are met, and

We have all used similar but distinct words interchangeably at times. It is easy to do and often times does not seem to matter. However, words and the message they deliver (whether intended or not) can be critical, especially in the area of clinical research.

With the new developments in immune effector cellular therapy and products recently approved by the FDA, such as Kymriah and Yescarta, it is even easier for the distinction between therapy and research to be blurred. These advances have been the focus of a lot of media attention, and laypeople may extrapolate the compelling human interest stories to any type of similar cellular therapy. Furthermore, some programs will be administering these commercial, licensed products to patients alongside research products. For other products still under research and not yet approved, staff must be aware of distinctions that must be clear to the prospective study subject.

In the United States, the Food and Drug Administration, Department of Health and Human Services, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, among others, have provided regulations and guidelines to ensure the protection of human subjects in research. Part of this protection involves the careful and intentional use of words when advertising for clinical trials, communicating with prospective study subjects, obtaining informed consent, and continues throughout the subject’s participation in a trial.

Words such as “treatment”, “patient”, and “cure”, when used in relation to participation in a clinical trial, can potentially blur the lines between treatment of a patient with an approveddrug and enrolling a subject in a clinical research study for the evaluation of safety and/or efficacy of a test article under investigation.

For individuals to be fully informed of research under which they are agreeing to participate, they must know that it is research and that the product is not yet an approved drug for the indication being evaluated. While it is possible that the test article may help or cure the disease, it is also possible that it may not improve the individual’s condition, may cause serious adverse reactions, or may even result in death.

Federal regulations provide additional safeguards for vulnerable populations, such as pregnant women, children, prisoners, mentally disabled, economically disadvantaged, and others. Vulnerable populations may also include the terminally ill given the gravity of their illness. There is a balance between increasing access to research trials for vulnerable populations and protecting these individuals from coercion or undue influence. Considering the relationship between a trusted physician and patient, and the hope for a cure of their illness, there is a fine line in clinical research for using accurate and intentional words to ensure full understanding, autonomy, and informed consent.

FACT Standards require reporting of adverse events related to cellular therapy product administration. FACT does not dictate the process or timing of such reporting, but requires that the reporting meets the requirements of applicable laws and regulations. We have fielded many questions via workshops, emails, and telephone calls regarding the reporting of adverse events related to commercial cellular therapy products (e.g., Kymriah, Yescarta).

Many stakeholders in the field are working on initiatives to make data reporting, including adverse event reporting, a more streamlined process. In the meantime, the FACT Immune Effector Cell Task Force recommends that programs define a reporting process and document it in a Standard Operating Procedure (SOP). The following are some tips for creating the process:

Know, understand, and comply with the reporting requirements outlined in the Risk Evaluation and Mitigation Strategies (REMS) for the specific product(s) you administer. List these requirements in the SOP.

For remaining gaps in the process, define your program’s reporting elements and frequency of reporting, including:

The types of adverse events that your program will report immediately (e.g., all events, specific grades of cytokine release syndrome) and to what source (e.g., MedWatch, manufacturer).

The types of adverse events that your program will collate for future reporting, the frequency of reporting such adverse events, and to whom the information will be reported.

Maintain documentation of all adverse events and reporting records.

Develop an audit plan and schedule for monitoring compliance with REMS requirements and the program-defined process.

Regularly check in with your manufacturer contacts for any updates to their adverse event reporting requirements.

In 2015, the FACT Technology Committee committed to replacing the FACTWeb Portal. This April, after three years, the first users logged into the new FACT Accreditation Portal. Ten different organizations were selected to serve as beta testers and complete their applications in the new portal.

Feedback on the new portal has been positive:

“So much faster than the old portal. It is nice that the tabs do not stay open as you move along the application. […] I generally am not a fan of being a beta site, but in this case, I am glad we are as this portal is such an improvement.”

“The new portal is so easy to work with and is a vast improvement from the previous system. It is much easier and quicker to go to the next question and to maneuver around in the portal. Thank you for your hard work in developing this new portal!”

“This is a major improvement over the first portal. The ease of use and the speed are complete upgrades! I appreciate everything that has been put into this new portal and realize that we will continue to strive to improve it. Very pleased to have been a beta tester!”

– Kim Kasow, UNC Bone Marrow Transplant and Cellular Therapy Program

With a successful beta test underway, the new FACT Accreditation Portal is scheduled for launch this August.

Upcoming Training Sessions

Online training opportunities are now available on the FACT Event Calendar. Advance registration is required. The first training session of each type will be recorded and made available online for on-demand viewing.

The first quarter of 2018 has been an exciting and busy one for the committee. Despite no meeting in February due to the BMT Tandem meetings, the committee was still able to review 13 programs for renewal accreditation in January and March 2018. Additionally, the committee reviewed the first program to apply for standalone accreditation under the FACT Standards for Immune Effector Cells.

The following are some notes regarding the function of the Cellular Therapy Accreditation Committee:

At each meeting, as deficiencies indicate potential needs for revisions or additions to future sets of FACT Standards, the issues are compiled into a list for future review by the Standards Committee. This feedback from the Cellular Therapy Accreditation Committee promotes improvement and greater clarity with each publication of Standards.

As programs complete the renewal accreditation process, in addition to the inspector’s assessment, they will be reviewed by the FACT-CIBMTR Data Audit Committee and possibly the Clinical Outcomes Improvement Committee. Recommendations related to data management and clinical outcome deficiencies are considered by the Cellular Therapy Accreditation Committee when determining the accreditation outcome for an applicant.

One of the most commonly cited requirements is validation. A satisfactory validation will include the following at a minimum:

An approved validation plan, including conditions to be validated

Acceptance criteria

Data collection

Evaluation of data

Summary of results

References, if applicable

Review and approval of the validation plan, validation report, and conclusion by the Quality Manager or designee and the Clinical Program Director/Facility Director or designee

The seventh edition of the FACT-JACIE Standards for Hematopoietic Cell Therapy was published at the beginning of March 2018. Programs must be compliant with this set of Standards by May 30, 2018. It is important for programs to remember that as they add new accredited services, such as immune effector cellular therapy or more than minimal processing, these must be implemented in compliance with the FACT Standards and reported to FACT. Additionally, if your program uses or plans to use contracted services in your organization, you are responsible for notifying FACT and monitoring the accreditation status of those service providers.

The FACT Common Standards Steering Committee convened at the BMT Tandem Meetings in February 2018 to finalize initial edits to the draft FACT Common Standards, second edition. A draft for public review and comment is scheduled for publication in June 2018.

The NetCord-FACT Standards Committee has begun its initial review of the draft NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration, seventh edition. The Cord Blood Committee roster can be found on the FACT website.

The NetCord-FACT Standards Steering Committee will complete the draft in September 2018. This draft will be made available for public review and comment.

It has been a long time coming, but now it is official. Full implementation of ISBT 128 coding and labeling is required of cellular therapy programs.

ICCBBA released an ISBT 128 compliance audit tool for use with cellular therapy products. The tool provides a means of determining compliance with the ISBT 128 Standard, and can be used by any cellular therapy facility around the world. It includes both interactive and printable audit checklists. FACT recommends use of this tool to verify correct implementation of ISBT 128 and to verify ongoing compliance. It may also be useful as an educational reference.

It is important to note that the tool does not take into consideration requirements from national regulatory bodies and may not cover all labeling requirements of cellular therapy accreditation bodies. Additionally, the tool does not ensure that proper Product Codes have been selected. Rather, it verifies correct placement and format of complete information.

Although ICCBBA has made validation tools available in the past, this is the first time an audit tool has been released. Input was received from industry experts and the international Cellular Therapy Coding and Labeling Advisory Group that is co-sponsored by ICCBBA, AABB, FACT, ISCT, and others. An instructional video is available on the ICCBBA website at www.iccbba.org.

The ASBMT Administrative Directors SIG Quality Working Group and the FACT Quality Management Committee are partnering on a project to identify opportunities to increase Quality Managers’ resiliency. The first step of this initiative was to develop a 59-question electronic survey, targeting HCT/CT/CBB Quality Managers, in order to collect data on their personal resilience and their perceptions of the benefits of improved resilience. Key takeaways from preliminary analysis indicate that:

• Strategic drivers for increasing Quality Manager resilience must be identified and deployed in order to recruit and retain proficient personnel who are both productive and able to support others in the program.
• Program administrators must understand the complexity and responsibility of the Quality Manager role and be engaged in supporting appropriate Quality Manager staffing levels, professional development and increased resiliency.

For complete details regarding the survey and its results, review the poster displayed at the 2018 BMT Tandem Meetings.

Email filters are critical to protecting business information systems, but, ironically, sometimes those filters can be overprotective and stop important messages from reaching your inbox.

In an effort to provide real-time, accessible, and environmentally and economically friendly information, FACT connects with its stakeholders from three main domains. All of these domains must be able to pass your email filters. If you received this newsletter via email, you likely do not have a problem. However, it is highly possible that your colleagues do. We strongly recommend you add FACT to the “white list” (sometimes referred to as a “safe list” or a “safe sender list”) of every colleague at your institution who should receive FACT information.

Emails generated from the FACT accreditation portal contain very important information, such as notifications, approval requests, and webpage links. The FACT store sends emails related to meeting registrations and online purchases, including free downloads. Newsletters, including this quarterly newsletter and weekly digests, provide information both critical and helpful for successfully achieving and maintaining compliance with FACT requirements.

Based on the security settings of your institution’s personnel accounts, it is possible that you will need to enlist the help of your Information Technology department. If you are able to whitelist email senders yourself, or if you use a personal email account for FACT correspondence, the following are helpful instructions:

After adding FACT’s domains to your whitelist, your email system may still attempt to filter FACT messages by sorting them into junk or clutter folders. If you do not receive an expected email from FACT and have already added us to your whitelist, check those folders. If ever in doubt, contact your FACT Accreditation Coordinator or the FACT office (fact@unmc.edu, 1-402-559-1950).

The following individuals completed their first active inspection in the time period from October 2017 through April 2018. Congratulations and thank you for volunteering your time and expertise to advance cellular therapy! Organizations with personnel who also serve as FACT inspectors typically perform better during on-site inspections than their counterparts without an inspector. If you are interested in serving as an inspector, submit an online application!

Full implementation of ISBT 128 labeling and coding is required by the seventh edition of the FACT-JACIE Hematopoietic Cellular Therapy Standards, which becomes effective this month. On Thursday, June 14, 2018, at 11:00 am ET, Dr. Phyllis I. Warkentin will discuss common questions about ISBT 128 terminology, product codes, FACT Standards, and regulatory requirements. Webinar participants will have a chance to ask Dr. Warkentin questions at the end of the presentation.

Join your cord blood colleagues for a day of presentations from renowned cord blood experts at the inaugural WMDA-NetCord & FACT Cord Blood Day! The event will be held in Miami, Florida on September 14, 2018, in conjunction with the Cord Blood Connect international congress.

The WMDA-NetCord & FACT Cord Blood Day will highlight issues that affect cord blood banks’ abilities to optimize processes within a challenging environment. The evolving demand for umbilical and cord blood products requires banks to consider changing indications and financial limitations on a continuous basis. Accreditation encourages implementation of efficient, quality-driven processes to meet these demands while banking products suitable for clinical administration.

Morning presentation topics include global perspectives of cord blood transplants, ethical dilemmas in cord blood banking, common FACT-NetCord accreditation citations, and an overview of the WMDA cord blood bank survey. The afternoon has two breakout sessions including a FACT inspector training track and a WMDA-NetCord & FACT cord blood quality boot camp track. We encourage banks to send multiple personnel to attend the various tracks as well as enlist a member to become a FACT inspector.

This is an excellent opportunity to network with the cord blood community and learn from experts in cord blood banking. Register by August 31 and save $135! Registration fees are waived for FACT active and trainee inspectors.

Completing an Annual/Renewal Report in the PortalApplicant Training Session Online

Join FACT’s IT Business Analyst for training on completing an annual or renewal report in the new FACT Accreditation Portal. Alisa Forsythe will discuss the navigation and features within the portal as well as the process for completing the application, the director approval process, and application submission. Webinar participants will have a chance to ask questions at the end of the presentation.

Completing a Compliance Application in the PortalApplicant Training SessionOnline

Join FACT’s IT Business Analyst for training on completing a compliance application in the new FACT Accreditation Portal. Alisa Forsythe will discuss the navigation and features within the portal as well as the process for completing the application, the director approval process, and application submission. Webinar participants will have a chance to ask questions at the end of the presentation.

Performing an Inspection in the Portal Inspector Training SessionOnline

Join FACT’s IT Business Analyst for training on performing an inspection in the new FACT Accreditation Portal. Alisa Forsythe will discuss the inspector specific navigation and features within the portal as well as the process for reviewing the applicant data, entering inspection findings, reviewing the inspection report, and submission. Webinar participants will have a chance to ask questions at the end of the presentation.